INDUCED SPUTUM AS A TOOL TO EVALUATE ANTI-INFLAMMATORY AGENTS IN CF PATIENTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。炎症有助于囊性纤维化(CF)肺部疾病的进展。交替使用皮质类固醇和每天两次大剂量布洛芬的抗炎治疗在CF患者中显示出临床益处，但不良反应和其他考虑因素明显限制了它们的使用。因此，设计一种评估预期抗炎药物的策略是非常可取的，它将只允许选择最有希望的药物进行第三阶段类型试验的进一步研究。另一个令人关注的问题是，由于没有早期的疗效指标，一些制药公司没有开发抗炎药来治疗慢性阻塞性肺疾病。这项研究将评估诱导痰中炎性介质的测量作为这样一种策略。需要检验的假设是，布洛芬和塞来昔布治疗4周后，将减少CF患者诱导痰中的中性粒细胞、活性弹性蛋白酶和促炎细胞因子。具体目的：确定高渗盐水诱导的痰中中性粒细胞、活性弹性蛋白酶和细胞因子是否为有用的筛查试验，以确定具有已知抗炎特性的特定药物是否适合进行更广泛的临床试验。这一目标将通过使用一种抗炎药布洛芬来实现，该药已被证明对CF具有临床益处。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Inflammation contributes to the progression of cystic fibrosis (CF) lung disease. Anti-inflammatory therapy with alternate-day corticosteroids and twice-daily high-dose ibuprofen in patients with CF has shown clinical benefit, but adverse effects and other considerations have markedly limited their use. Thus, it is highly desirable to design a strategy for evaluation of prospective anti-inflammatory agents that will allow for the selection of only the most promising agents for further study in Phase III type trials. Of additional concern is the fact that some pharmaceutical firms have not pursued development of anti-inflammatory agents for CF because there were no early indicators of efficacy. This study will assess the measurement of inflammatory mediators in induced sputum as one such strategy. The hypothesis to be tested is that ibuprofen and celecoxib will reduce neutrophils, active elastase, and proinflammatory cytokines in induced sputum after 4 weeks of therapy in patients with CF. Specific Aim: To determine whether neutrophils, active elastase, and cytokines measured in sputum induced using hypertonic saline are useful screening tests for determining if a particular agent with known anti-inflammatory properties is a suitable candidate for more extensive clinical trials in patients with CF. This aim will be addressed using one anti-inflammatory agent, ibuprofen, that has been shown to have clinical benefit in CF.